La radiologia medica

, Volume 123, Issue 3, pp 202–208 | Cite as

Abnormal cervical lymph nodes in multiple sclerosis: a preliminary ultrasound study

  • Francesca Di Giuliano
  • Maria Albanese
  • Eliseo PicchiEmail author
  • Francesco Mori
  • Fabio Buttari
  • Girolama Alessandra Marfia
  • Francesco Garaci
  • Nicola Biagio Mercuri
  • Roberto Floris
  • Diego Centonze
  • Simone Marziali



Cervical lymph nodes are the first drainage stations of the brain and therefore play a key role in neuroinflammatory disorders such as multiple sclerosis.


The aim of this study was to evaluate, by using ultrasound imaging, cervical lymph nodes in patients with multiple sclerosis and to ascertain if such patients have any clinical features to attest their role.


We enrolled 43 patients affected by relapsing–remitting multiple sclerosis (22 drug free and 21 under treatment with natalizumab or fingolimod), who underwent ultrasound examination. The morphology, diameters and volume of cervical lymph nodes were measured. We evaluated also a control group of 20 healthy volunteers.


Between-group comparisons showed that the mean anteroposterior diameters in the cervical lymph nodes on both sides of the neck were significantly different (χ 2 = 19.5, p < 0.001 for right; χ 2 = 20.0, p < 0.001 for left). Post hoc contrasts showed that the mean anteroposterior diameters were greater both in drug-naive (mean ± SD 0.66 ± 0.20 cm; p < 0.001) and treated patients (0.55 ± 0.24 cm; p < 0.001) compared to healthy individuals (0.36 ± 0.19 cm). Moreover, significant difference (p < 0.001) was shown on comparing the mean volume of the cervical lymph nodes on both sides of the neck in the studied groups. No significant differences emerged between the drug-free and treated patients.


The abnormalities shown by ultrasound in cervical lymph nodes are related to deep ones and independent of the ongoing treatment, suggesting a relationship between lymphatic drainage and disease pathology.


Cervical lymph nodes Multiple sclerosis Ultrasound 


Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.


This study has not received grant or funding.

Informed consent

Informed consent was obtained from all individual participants included in the study.


  1. 1.
    Weller RO, Djuanda E, Yow HY, Carare RO (2009) Lymphatic drainage of the brain and the pathophysiology of neurological disease. Acta Neuropathol (Berl) 117(1):1–14. CrossRefGoogle Scholar
  2. 2.
    Liu NF, Lu Q, Jiang ZH, Wang CG, Zhou JG (2009) Anatomic and functional evaluation of the lymphatics and lymph nodes in diagnosis of lymphatic circulation disorders with contrast magnetic resonance lymphangiography. J Vasc Surg 49(4):980–987. CrossRefPubMedGoogle Scholar
  3. 3.
    Girard JP, Moussion C, Förster R (2012) HEVs, lymphatics and homeostatic immune cell trafficking in lymph nodes. Nat Rev Immunol 12(11):762–773. CrossRefPubMedGoogle Scholar
  4. 4.
    Schneider M, Ny A, Ruiz de Almodovar C, Carmeliet P (2006) A new mouse model to study acquired lymphedema. PLoS Med 3(7):e264. CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Phillips MJ, Needham M, Weller RO (1997) Role of cervical lymph nodes in autoimmune encephalomyelitis in the Lewis rat. J Pathol 182(4):457–464.<457:AID-PATH870>3.0.CO;2-Y CrossRefPubMedGoogle Scholar
  6. 6.
    Cohen JA, Chun J (2011) Mechanisms of fingolimod’s efficacy and adverse effects in multiple sclerosis. Ann Neurol 69(5):759–777. CrossRefPubMedGoogle Scholar
  7. 7.
    Rennels ML, Gregory TF, Blaumanis OR, Fujimoto K, Grady PA (1995) Evidence for a “paravascular” fluid circulation in the mammalian central nervous system, provided by the rapid distribution of tracer protein throughout the brain from the subarachnoid space. Brain Res 326(1):47–63CrossRefGoogle Scholar
  8. 8.
    Rennels ML, Blaumanis OR, Grady PA (1990) Rapid solute transport throughout the brain via paravascular fluid pathways. Adv Neurol 52:431–439PubMedGoogle Scholar
  9. 9.
    Cserr HF, Harling-Berg CJ, Knopf PM (1992) Drainage of brain extracellular fluid into blood and deep cervical lymph and its immunological significance. Brain Pathol 2(4):269–276CrossRefPubMedGoogle Scholar
  10. 10.
    Iliff JJ, Wang M, Liao Y et al (2012) A paravascular pathway facilitates CSF flow through the brain parenchyma and the clearance of interstitial solutes, including amyloid ß. Sci Transl Med 4(147):147ra111. CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Yang L, Kress BT, Weber HJ et al (2013) Evaluating glymphatic pathway function utilizing clinically relevant intrathecal infusion of CSF tracer. J Transl Med 11:107. CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Foldi M, Csanda E, Obal F, Madarasz I, Zoltan OT, Szeghy G (1963) On effects of ligation of the lymphatic vessels and lymph nodes of the neck on the central nervous system in animal experiments. Z Gesamte Exp Med 137:483–510CrossRefGoogle Scholar
  13. 13.
    Kida S, Pantazis A, Weller RO (1993) CSF drains directly from the subarachnoid space into nasal lymphatics in the rat. Anatomy, histology and immunological significance. Neuropathol Appl Neurobiol 19(6):480–488CrossRefPubMedGoogle Scholar
  14. 14.
    Johnston M, Zakharov A, Papaiconomou C, Salmasi G, Armstrong D (2004) Evidence of connections between cerebrospinal fluid and nasal lymphatic vessels in humans, non-human primates and other mammalian species. Cerebrospinal Fluid Res 1(1):2. CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Johnston M, Zakharov A, Koh L, Armstrong D (2005) Subarachnoid injection of Microfil reveals connections between cerebrospinal fluid and nasal lymphatics in the non-human primate. Neuropathol Appl Neurobiol 31(6):632–640. CrossRefPubMedGoogle Scholar
  16. 16.
    Nagra G, Koh L, Zakharov A, Armstrong D, Johnston M (2006) Quantification of cerebrospinal fluid transport across the cribriform plate into lymphatics in rats. Am J Physiol Regul Integr Comp Physiol 291(5):R1383–R1389. CrossRefPubMedGoogle Scholar
  17. 17.
    Zhang ET, Richards HK, Kida S, Weller RO (1992) Directional and compartmentalised drainage of interstitial fluid and cerebrospinal fluid from the rat brain. Acta Neuropathol (Berl) 83(3):233–239CrossRefGoogle Scholar
  18. 18.
    Louveau A, Smirnov I, Keyes TJ et al (2015) Structural and functional features of central nervous system lymphatic vessels. Nature 523(7560):337–341. CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Aspelund A, Antila S, Proulx ST et al (2015) A dural lymphatic vascular system that drains brain interstitial fluid and macromolecules. J Exp Med 212(7):991–999. CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Weller RO (2005) Microscopic morphology and histology of the human meninges. Morphologie 89(284):22–34CrossRefPubMedGoogle Scholar
  21. 21.
    Decimo I, Fumagalli G, Berton V, Krampera M, Bifari F (2012) Meninges: from protective membrane to stem cell niche. Am J Stem Cell 1(2):92–105Google Scholar
  22. 22.
    Steinkamp HJ, Cornehl M, Hosten N, Pegios W, Vogl T, Felix R (1995) Cervical lymphadenopathy: ratio of long- to short-axis diameter as a predictor of malignancy. Br J Radiol 68(807):266–270. CrossRefPubMedGoogle Scholar
  23. 23.
    Fabriek BO, Zwemmer JN, Teunissen CE et al (2005) In vivo detection of myelin proteins in cervical lymph nodes of MS patients using ultrasound-guided fine-needle aspiration cytology. J Neuroimmunol 161(1–2):190–194. CrossRefPubMedGoogle Scholar
  24. 24.
    Rangroo Thrane V, Thrane AS, Plog BA et al (2013) Paravascular microcirculation facilitates rapid lipid transport and astrocyte signaling in the brain. Sci Rep 3:2582. CrossRefPubMedGoogle Scholar
  25. 25.
    Plog BA, Dashnaw ML, Hitomi E et al (2015) Biomarkers of traumatic injury are transported from brain to blood via the glymphatic system. J Neurosci 35(2):518–526. CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Sospedra M, Martin R (2005) Immunology of multiple sclerosis. Annu Rev Immunol 23:683–747. CrossRefPubMedGoogle Scholar
  27. 27.
    Gadani SP, Walsh JT, Lukens JR, Kipnis J (2015) Dealing with danger in the CNS: the response of the immune system to injury. Neuron 87(1):47–56. CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Urra X, Miró F, Chamorro A, Planas AM (2014) Antigen-specific immune reactions to ischemic stroke. Front Cell Neurosci 12(8):278. Google Scholar

Copyright information

© Italian Society of Medical Radiology 2017

Authors and Affiliations

  1. 1.Department of Biomedicine and PreventionUniversity of Rome “Tor Vergata”RomeItaly
  2. 2.Department of Diagnostic and Molecular Imaging, Interventional Radiology and Radiotherapy, Neuroradiology UOCFondazione PTV Policlinico “Tor Vergata”RomeItaly
  3. 3.Multiple Sclerosis Clinical and Research Unit, Department of Systems MedicineUniversity of Rome “Tor Vergata”RomeItaly
  4. 4.Neurology Unit, Department of NeurosciencesFondazione PTV Policlinico “Tor Vergata”, University of Rome “Tor Vergata”RomeItaly
  5. 5.IRCCS Istituto Neurologico Mediterraneo (INM) NeuromedPozzilliItaly
  6. 6.IRCCS Fondazione Santa LuciaRomeItaly

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